As both men and mice age, their immune systems lose their ability to function normally. My first objective is to find out in mice how much of that loss is intrinsically timed within lymphoid stem cell lines and lymphoid organ microenvironments; and how much immunologic activity is lost because it cannot be adequately supported in the aged mouse's deficient internal environment. To answer these questions, lymphoid stem cell lines and intact lymphoid organs are transplanted from old mice (and from young adult controls) into histocompatible young recipients. The ability of these transplants to perform immunologic functions is tested rigorously in systems where the transplants are clearly identified. My second objective is to determine whether aging of the immune response allows more cancers to develop. Cancers that develop spontaneously with increased incidences in aging mice will be tested to determine how strongly they stimulate immune responses against themselves. Cancers from older mice will tend to stimulate stronger immune responses if immunological loss with age has allowed tumors to grow that younger mice would have rejected. My third objective is to rejuvenate immune responses in old mice. Young stem cell lines and intact young lymphoid organs will be transplanted into old mice; young mice will be parabiosed to old mice by joining their skins, and chromosome markers will identify old and young cells. Immune functions and other parameters that change with age will be followed. Life span and pathology at death will be compared between the old mice that we attempt to rejuvenate, and matched untreated old controls.